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Blocking p38 Signaling Reduces the Activation of Pro-inflammatory Cytokines and the Phosphorylation of p38 in the Habenula and Reverses Depressive-Like Behaviors Induced by Neuroinflammation
Zhao, Ya-wei1,2; Pan, Yu-qin1,2; Tang, Ming-ming1; Lin, Wen-juan1,2
2018-05-15
Source PublicationFRONTIERS IN PHARMACOLOGY
Correspondent Emaillinwj@psych.ac.cn
ISSN1663-9812
SubtypeArticle
Volume9Pages:1-14
Contribution Rank1
Abstract

Increasing evidence has demonstrated that neuroinflammation contributes to the development of depressive-like behaviors, in both animal models and human patients; however, the brain areas and signaling pathways involved are still elusive. Recent studies have suggested novel roles of the habenula in the onset of depression and other psychiatric disorders, however, there is no evidence for whether the habenula has a function in neuroinflammation-induced depression. Using an animal model of depression, which is induced by the repeated central administration of lipopolysaccharide (LPS), we examined whether cytokine expression and p38 signal activation in the habenula were involved in the depressive-like behaviors. Body weight, saccharin preference test, and tail suspension test were used to measure depressive-like behaviors Immunohistochemistry, quantitative-polymerase chain reaction (q-PCR), and western blot were used to measure the expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), and the phosphorylation of p38 in the habenula. The results showed that central LPS administration induced depressive-like behaviors, characterized by anhedonia in the saccharin preference test and increased immobility in the tail suspension test Central LPS administration also significantly increased the p-p38 level in microglial cells and increased TNF-a expression in the habenula. Treatment with fluoxetine, a widely prescribed antidepressant, or SB203580, a p38-specific inhibitor, reversed the depressive-like behaviors, normalized the alterations in p-p38 and TNF-a levels and increased the levels of the anti-inflammatory cytokine IL-10 in the habenula The present findings suggest that the habenula is involved in the pathophysiology of behavioral depression induced by neuroinflammation, and the p38 pathway may serve as a novel mechanism-based target for the treatment of inflammation-related depression.

Keyworddepression p38 neuroinflammation habenula fluoxetine SB203580
DOI10.3389/fphar.2018.00511
Indexed BySCI ; SSCI
Language英语
Funding OrganizationNational Natural Science Foundation of China(31170987 ; CAS Key Laboratory of Mental Health, Institute of Psychology(KLMH20142G01) ; 31440045)
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000432304200003
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS KeywordGLUCOCORTICOID-RECEPTOR FUNCTION ; INDUCED AIRWAY INFLAMMATION ; MAJOR DEPRESSION ; LATERAL HABENULA ; PROTEIN-KINASE ; MAP KINASE ; MEDIAL HABENULA ; RATS ; MODEL ; LIPOPOLYSACCHARIDE
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Cited Times:1[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/26196
Collection中国科学院心理健康重点实验室
Affiliation1.Chinese Acad Sci, Inst Psychol, Key Lab Mental Hlth, Beijing, Peoples R China
2.Univ Chinese Acad Sci, Dept Psychol, Beijing, Peoples R China
First Author AffilicationKey Laboratory of Mental Health, CAS
Recommended Citation
GB/T 7714
Zhao, Ya-wei,Pan, Yu-qin,Tang, Ming-ming,et al. Blocking p38 Signaling Reduces the Activation of Pro-inflammatory Cytokines and the Phosphorylation of p38 in the Habenula and Reverses Depressive-Like Behaviors Induced by Neuroinflammation[J]. FRONTIERS IN PHARMACOLOGY,2018,9:1-14.
APA Zhao, Ya-wei,Pan, Yu-qin,Tang, Ming-ming,&Lin, Wen-juan.(2018).Blocking p38 Signaling Reduces the Activation of Pro-inflammatory Cytokines and the Phosphorylation of p38 in the Habenula and Reverses Depressive-Like Behaviors Induced by Neuroinflammation.FRONTIERS IN PHARMACOLOGY,9,1-14.
MLA Zhao, Ya-wei,et al."Blocking p38 Signaling Reduces the Activation of Pro-inflammatory Cytokines and the Phosphorylation of p38 in the Habenula and Reverses Depressive-Like Behaviors Induced by Neuroinflammation".FRONTIERS IN PHARMACOLOGY 9(2018):1-14.
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